title: Biophysical and pharmacological characterization of voltage-dependent Ca2+ channels in neurons isolated from rat nucleus accumbens.
abstract: The nucleus accumbens (NA) has an integrative role in behavior and may mediate addictive and psychotherapeutic drug action. Whole cell recording techniques were used to characterize electrophysiologically and pharmacologically high- and low-threshold voltage-dependent Ca2+ currents in isolated NA neurons. High-threshold Ca2+ currents, which were found in all neurons studied and include both sustained and inactivating components, activated at potentials greater than -50 mV and reached maximal activation at approximately 0 mV. In contrast, low-threshold Ca2+ currents activated at voltages greater than -64 mV with maximal activation occurring at -30 mV. These were observed in 42% of acutely isolated neurons. Further pharmacological characterization of high-threshold Ca2+ currents was attempted using nimodipine (Nim), omega-conotoxin-GVIA (omega-CgTx) and omega-agatoxin-IVA (omegaAga), which are thought to identify the L, N, and P/Q subtypes of Ca2+ currents, respectively. Nim (5-10 muM) blocked 18%, omegaCgTx (1-2 muM) blocked 25%, and omegaAga (200 nM) blocked 17% of total Ca2+ current. Nim primarily blocked a sustained high-threshold Ca2+ current in a partially reversible manner. In contrast, omegaCgTx irreversibly blocked both sustained and inactivating components. omegaAga irreversibly blocked only a sustained component. In all three of these Ca2+ channel blockers, plus 5 muM omega-conotoxin-MVIIC to eliminate a small unblocked Q-type Ca2+ current (7%), a toxin-resistant high-threshold Ca2+ current remained that was 32% of total Ca2+ current. This current inactivated much more rapidly than the other high-threshold Ca2+ currents, was depressed in 50 muM Ni2+ and reached maximal activation 5-10 mV negative to the toxin-sensitive high-threshold Ca2+ currents. Thus NA neurons have multiple types of high-threshold Ca2+ currents with a large component being the toxin-resistant "R" component.
authors.affiliation: Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Alberta T2N 4N1, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Churchill
authors.forename: B A
authors.initials: BA
authors.lastname: Macvicar
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009553:Nimodipine / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000166:cytology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D009553:Nimodipine; D020866:omega-Conotoxin GVIA; D002118:Calcium